Thumb carpometacarpal (CMC) osteoarthritis (OA) is a widespread, disabling disease that is far more prevalent in woman than men. The disease affects 15% of adults over age 30, and two-thirds of women over the age of 55. While the pathophysiology of osteoarthritis is considered to be multifactorial, abnormal joint kinematics and altered cartilage contact are believed to trigger and sustain the disease via the production of non-physiologic contact stresses, which in turn lead to chondrocyte derangement, necrosis, and cartilage degradation. However, at this point there is only limited data on thumb CMC joint biomechanics in normal or OA-affected individuals, and there are no longitudinal studies of joint biomechanics as the disease progresses. Accordingly, the broader, long-term objective of this study is to explore the role of biomechanics and morphology in basilar thumb joint osteoarthritis in an effort to identify biomechanical markers for the initiation and progression of the disease that will ultimately improve prognosis and treatment. The specific objective of the work outlined in this application is to follow disease progression longitudinally in a existing cohort of thumb CMC OA patients, acquiring biomechanical, radiographic, and clinical data at 4.5- and 6-year follow-ups using our innovative techniques, as a follow-on to data collected at baseline (0 yr), 1.5 and 3 years, during the previous funding cycle. Evaluation of the role of biomechanics and morphology in basilar thumb joint osteoarthritis will be accomplished via two specific aims. Aim 1 will evaluate joint instability as a potential marker for thumb CMC OA progression in an existing cohort of women and men who presented with early stage CMC OA (pain but no gross radiographic changes). Aim 2 will determine if the rate of thumb CMC OA progression in women is greater than in men, and if any differential rate of disease progression is associated with corresponding differences in joint instability and bone shape changes. Both aims will be evaluated via long-term follow-up of 85 early OA patients. Innovative biomechanical markers and standardized clinical outcome measures will be used to address the hypotheses outlined in each aim. At each follow-up visit (years 4.5 and 6) CMC joint motion (arthrokinematics) and instability during three high-demand tasks will be assessed with our state-of-art computed tomography-based markerless bone registration techniques. Wrist/hand-directed histories and physical exams will also be obtained, as will quantitative assessments of thumb range of motion and strength, three sets of standardized patient-reported functional assessments, and plain radiographs, using the same protocols and survey instruments used during the previous funding cycle. The significance of this proposal is the long-term longitudinal study and the identification of biomechanical markers for CMC OA progression. This information is crucial for future basic and clinical research studies and for the rational design of innovative new strategies for prevention and treatment.